title: Pharmacological distinction between soluble and transmembrane adenylyl cyclases.
abstract: The second messenger cAMP is involved in a number of cellular signaling pathways. In mammals, cAMP is produced by either the hormonally responsive, G protein-regulated transmembrane adenylyl cyclases (tmACs) or by the bicarbonate- and calcium-regulated soluble adenylyl cyclase (sAC). To develop tools to differentiate tmAC and sAC signaling, we determined the specificity and potency of commercially available adenylyl cyclase inhibitors. In cellular systems, two inhibitors, KH7 and catechol estrogens, proved specific for sAC, and 2',5'-dideoxyadenosine proved specific for tmACs. These tools provide a means to define the specific contributions of the different families of adenylyl cyclases in cells and tissues, which will further our understanding of cell signaling.
authors.affiliation: Department of Pharmacology, Weill Cornell Medical College, New York, New York.
authors.forename: Jacob L
authors.initials: JL
authors.lastname: Bitterman
authors.forename: Lavoisier
authors.initials: L
authors.lastname: Ramos-Espiritu
authors.forename: Ana
authors.initials: A
authors.lastname: Diaz
authors.forename: Lonny R
authors.initials: LR
authors.lastname: Levin
authors.forename: Jochen
authors.initials: J
authors.lastname: Buck
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D013379:Substrate Specificity
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D000242:Cyclic AMP; C579271:ADCY10 protein, human; D000262:Adenylyl Cyclases